Over the past twenty five years, the quality of life for many people has been dramatically improved due to advances in replacing damaged or diseased organs. Many new materials have been developed for medical applications intended for use in contact with or implanted within the body. e.g. bone and joint replacements, hemodialysis devices, artificial hearts, and soft contact lenses. The overall requirements for such materials are quite demanding. They must function within the body environment, and be stable, non toxic, and not elicit any adverse host reaction. Most are synthetic polymers, while some more recently developed biomaterials consist of chemically modified tissues.
An important distinction must be made between organ transplants and the application of a biomaterial. Transplants consist of viable tissue either autotransplanted within the same organism (e.g. skin grafts or saphenous vein arterial replacements) or used from one organism to another (e.g. kidney or heart transplants). Biomaterials are generally non-viable materials produced in the laboratory and intended for medical device construction.
Both synthetics and tissue based materials have their advantages and disadvantages. The properties of synthetic polymers may be readily modified by altering monomers or reaction conditions. Polymers are easily fabricated and generally have acceptably low biological responses. For critical blood contacting applications however (e.g. small diameter arterial replacement and cardiac valves), plastic materials all exhibit unacceptable thrombogenicity. Tissue biomaterials have shown superior blood contacting properties, but suffer from being more difficult to fabricate into devices and possess inferior in vivo stability. Incomplete crosslinking of these tissues, particularly the collagen matrix, can lead to enhanced biodegradation, antigenicity, and loss of mechanical function.
The current invention addresses these two important aspects of tissue materials: biophysical stability and ease of fabrication. Research was conducted using bovine peritoneum as a tissue source. Methods of achieving greater collagen crosslinking were investigated. To facilitate device construction, a simple method is described for bonding tissue to synthetic substrates. These substrates may be attached to other metal or plastic systems by conventional means.
The processing techniques generally used to produce tissue biomaterials involves stabilizing the structure to prevent resorption and tissue rejection following reimplantation. Stabilization involves crosslinking the collagenous component of the tissue usually using glutaraldehyde (GA). This is a crucial step in the preparation of the biomaterial, as the ultimate fate of the tissue is related to the fixatives, fixation conditions, and the condition of the raw starting material.
It is important to process the tissue while it is still fresh. Autolytic and bacterial degradation can proceed to the point that the tissue may be incapable of being sufficiently stabilized. These effects have generally not received appropriate attention, as current manufacture of tissue materials allows significant latitude in the collection and storage of fresh tissue prior to stabilization.
Early attempts at replacing blood vessels in man involved the use of solid walled rigid tubes of metal and acrylics (1). These grafts did not perform well in most cases. The modern era of synthetic vascular grafts was initiated by the use of Vinyon cloth tubes (2). Present day synthetic grafts are used in diameters down to 6-8 mm and are mainly fabricated from Dacron* polyester fiber and expanded Teflon* (polytetraflouroethylene) (3). FNT (* Registered Trade Marks)
For arterial replacement below 6-8 mm, biologic vascular grafts have proven more successful. Grafts have been prepared from bovine carotid artery, human umbilical veins, and bovine ureters by a variety of chemical methods. The long term durability of these grafts however is currently an issue of concern, with failure rates and complications rising after 3-5 years (4).
For constructing heart valves and other applications, material in the form of a flat sheet or membrane is required. Stabilized calf and porcine aortic valves were introduced for clinical use in 1965 as an alternate to the more thrombogenic mechanical devices (5). Formalin was used for stabilization, and these valves underwent gross degeneration of the collagen fibers and led to aortic insufficiency. In 1969, GA was introduced as a tanning agent, which proved to be a better stabilizing agent, making the valve tissue pratically inert and nonantigenic. At present, the more commonly used vascular grafts and valve xenografts use GA for their primary fixation.
Pericardium is currently the most widely used xenograft membrane material for cardiovascular applications. The pericardial xenograft valve was introduced in 1974 (6), with several new generation devices at various stages of development including the Hancock, low-profile Ionescu-Shiley, Carpentier-Edwards, and Mitral Medical valves. Despite their superior hydraulic and blood contacting properties, tissue valves continue to have calcification and durability problems (7).
In an effort to reduce or eliminate these complications, research was conducted into finding alternate tissue sources, improved chemical fixation methods, and methods to improve device construction.
The present invention relates to the use of peritoneal tissue for producing a new biomaterial. The materials produced have advantageous biological and structural properties relative to existing xenograft materials; including flexibility and the presence of two smooth surfaces.
It is an object of the invention to provide an improved biomaterial suitable for bioprosthesis fabrication, and methods for producing same.
It is another object to,
(1) provide improved methods for collagen crosslinking, and (2) provide methods for producing a composite tissue/synthetic material.
The peritoneum is the largest serous membrane in the body. The membrane lines the abdominal walls (parietal peritoneum) and also invests the contained viscera. The free surface is lined with a single layer of mesothelial cells, lying above an elastic membrane and subjacent connective tissue layers.
Peritoneum has been surgically transplanted into different physiological systems with general success. Free grafts have been used to cover defects in the renal pelvis (8) and to reinforce alimentary trace anastomoses (9). As an aortic patch graft in dogs (10), good healing was observed with no ruptures, occlusions, or aneurysms. Autogenous peritoneum has also been used for cardiac valve replacement in dogs (11). The grafts did not function well in the long term due to thickening and contraction, but did show acceptable short term blood compatibility.